[Results analysis of mNGS applied to infectious diseases].

The application of metagenomic second-generation sequencing (mNGS) is shifting from research to clinical laboratories due to rapid technological advances and significant cost reductions. Although many studies and case reports have confirmed that the success of mNGS in improving the prevention, diagnosis, treatment and tracking of infectious diseases, there are still some obstacles that must be overcome. The results of mNGS show all the possible pathogens in the sample, however, in the face of thousands of microbes that can infect humans, it remains challenging to accurately identify the key pathogens. So far, there is no unified interpretation standard for mNGS in clinical practice. This article reviews the interpretation of mNGS results for pathogen infection in different systems, the clinical interpretation and application regulations of mNGS results, and the challenges of mNGS interpretation in pathogen diagnosis.

Efficacy and safety of PD1/PDL1 inhibitors combined with radiotherapy and antiangiogenic drugs for hepatocellular carcinoma: a systematic review and meta-analysis.

OBJECTIVE: The triplet regimen based on the programmed cell death 1 (PD1)/ programmed cell death ligand 1 (PDL1) inhibitors combined radiotherapy and antiangiogenic drugs is a novel therapeutic strategy for hepatocellular carcinoma. We conducted a meta-analysis to evaluate the efficacy and safety of the triplet therapeutic regimen in the treatment of hepatocellular carcinoma. MATERIALS AND METHODS: We searched scientific literature databases and clinical trial databases through October 31, 2022, for required studies. The pooled hazard ratio (HR) was used to analyze the overall survival (OS), progression-free survival (PFS), and the pooled relative risk (RR) was used to analyze the objective response rate (ORR), disease control rate (DCR), mortality rate (MR), and adverse events (AEs) through random or fixed effects model, 95% confidence interval (CI) was determined for all outcomes. Qualities of the included literature were assessed by MINORS Critical appraisal checklist. Funnel plot was used to assess publication bias in the included studies. RESULTS: Five studies (3 single-arm and 2 non-randomized comparative trials), including 358 cases, were enrolled. Meta-analysis showed that the pooled ORR, DCR, and MR were 51% (95% CI: 34%-68%), 86% (95% CI: 69-102%), and 38% (95% CI: 18-59%), respectively. Compared with triplet regimen, the single or dual-combination treatments had shorter OS (HR=0.53, 95%: 0.34-0.83 via univariate analysis; HR=0.49, 95%: 0.31-0.78 via multivariable analysis) and PFS (HR=0.52, 95%: 0.35-0.77 via univariate analysis; HR=0.54, 95%: 0.36-0.80 via multivariable analysis). Common AEs to triplet regimens included skin reaction (17%), nausea/vomiting (27%), fatigue (23%), while severe AEs (10%), fever (18%), diarrhea (15%), and hypertension (5%) without statistically significant differences. CONCLUSIONS: In the treatment of hepatocellular carcinoma, PD1/PDL1 inhibitors combined radiotherapy and antiangiogenic drugs achieved better survival benefits than alone or dual-combination regimens. In addition, the triple-combination therapy has tolerable safety.

[Comparison and application of postprandial and fasting blood lipid levels in 839 physical examinees in Beijing].

Objective: To investigate the feasibility of application of non-fasting dyslipidemia cutoff values in community population. Methods: Self-control study was used. 839 physical examinees (292 males and 547 females) were recruited in clinical laboratory of Guang'an men Hospital from January to October 2018. The median (interquartile range) of age was 60 (54, 66) years. Blood samples were collected before and at 4 h after a standard breakfast. Comparison of fasting and postprandial lipoprotein levels was performed using Paired-Samples T Test or Two-Related-Samples Wilcoxon. The changes of 4-hour postprandial blood lipid levels and the percentages of postprandial dyslipidemia according to different stratification of fasting dyslipidemia were performed using one-way ANOVA and χ2 test, respectively. Results: Compared with fasting, 4-hour postprandial total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), non-high density lipoprotein cholesterol (non-HDL-C), apolipoprotein A1 (ApoA1) and apolipoprotein B (ApoB) decreased slightly, postprandial triglyceride (TG) increased by 0.72 mmol/L, and postprandial remnant-like lipoprotein cholesterol (RLP-C) increased by 0.27 mmol/L (t or Z values = 10.26,22.94,24.22,4.71,16.61,26.92,-23.58,-19.35, P<0.05, respectively). According to the non-fasting dyslipidemia cut-off values recommended by the European consensus, there were 10%, 16.6%, 10.1%, 12.3%, 30% and 34.9% of the population in the appropriate levels of fasting TC, LDL-C, HDL-C, non-HDL-C, TG and RLP-C distributed in elevated levels of postprandial, respectively. The changes of 4-hour postprandial TC, LDL-C, non-HDL-C and HDL-C increased with the elevation of fasting level (F=9.50,6.18,8.07,3.86,P<0.01), and the maximum changes of TC≤3.5%, LDL-C≤6.8%, non-HDL-C≤2.9%, HDL-C≤6.3%; the change of 4-hour postprandial TG increased slightly first and then decreased significantly (51.3% vs. 57.9% vs. 39.2%, F=19.05, P<0.01); the change of 4-hour postprandial RLP-C decreased (50.8% vs. 33.2%, F=10.40, P<0.01). The cut-off values of 4-hour postprandial dyslipidemia were TC ≥5.1 mmol/L, LDL-C ≥3.2 mmol/L, HDL-C ≤0.9 mmol/L, non-HDL-C ≥4.0 mmol/L and RLP-C ≥1.0 mmol/L. The cut-off values of borderline elevated and elevated TG levels were ≥2.2 mmol/L and ≥3.4 mmol/L, respectively. Conclusions: The cut-off values of postprandial dyslipidemia including TC, LDL-C, HDL-C, non-HDL-C and RLP-C were preliminarily established in community population, which could be applied to the routine lipid profile evaluation in the physical examination population. And it might be needed that postprandial TG was managed hierarchically according to different cut-off values.

[Analysis of HBsAg screening among rural childbearing age people in Yunnan province during 2013-2017].

Objective: To explore the current status of HBV infection before pregnancy among rural childbearing age people in Yunnan province, find out the population at high risk and areas with high incidence and provide evidence for promoting pre-pregnancy aristogenesis and medical interventions for prevention of HBV infection. Methods: The subjects in the study were rural childbearing age people aged 18-49 who received the national free pre pregnancy eugenic health examination in Yunnan province during 2013-2017. Descriptive analysis was conducted for HBsAg positive rate and its difference among various characteristics. The SPSS 22.0 software was used for statistical analysis. Results: A total of 2 180 841 rural childbearing age people were surveyed, the HBsAg positive rate before pregnancy was 3.13%(68 314/2 180 841) in Yunnan. And the HBsAg positive rate was 3.56% (37 694/1 057 376) in men, higher than that in women (2.73%, 30 620/1 123 465). The HBsAg positive rate was highest in age group 41-49 years (3.77%, 3 126/82 931). The HBsAg positive rate was higher in minority ethnic group (3.77%, 27 974/742 518) than in Han ethnicity group (2.81%, 40 024/1 425 870). Moreover, the highest HBsAg positive rate of was 8.20%(851/10 378) in Yao ethnic group. The people with education level of primary education had the highest HBsAg positive rate (3.97%, 17 294/435 219). The HBsAg positive rate was highest in Xishuangbanna Dai autonomous prefecture (6.65%, 3 875/58 232) in Yunnan. Moreover, the HBsAg positive population in severe poor area (3.32%, 19 755/595 665) was higher than those in less poor area (3.17%, 29 750/939 101) or normal areas (2.91%, 18 809/646 075). There was significant difference in HBsAg positive rate among populations in different age groups, ethnic groups, education level groups, areas and economic level groups (P<0.001). Conclusions: The HBsAg positive rate in rural childbearing age people in Yunnan was related to multi factors, including sex, age, ethnic group, education level, area and economic development level. The HBsAg positive rate was higher in men, older age and lower education level, minority ethnic group (especially in Yao ethnic group), from Xishuangbanna prefecture and the poor living conditions in childbearing age population.

[Serum bone turnover markers and vitamin D level in diabetes patients with and without tuberculosis].

Objective: To investigate the levels of bone turnover marks and vitamin D(25OHD(3))in diabetes patients with and without tuberculosis. Methods: A total of 163 patients were recruited from Beijing Hospital and Jilin Provincial Academy of Tuberculosis Control and Prevention. including 80 diabetes patients without tuberculosis [39 males and 41 females, mean age (59±10) years], and 83 diabetes patients with tuberculosis [34 males and 49 females, mean age (56±12) years]. In the meantime, 80 healthy subjects were recruited as the normal control [39 males and 41 females, mean age (50±8) years]. The blood samples of all participants were taken after 10 hours fasting and before anti-tuberculosis treatment, and the levels of 25OHD(3), ß-crossLaps, Osteocalcin(OCN), and total procollagen type 1 amino-terminal propeptide(tP(1)NP) were meausured. One-way ANOVA and chis-square test were used for comparisons among the 3 groups and between groups respectively. Results: The concentration of 25OHD(3) was higher in diabetes patients without tuberculosis (16 µg/L) than in those with tuberculosis (14 µg/L), P<0.05, but significantly lower than that in the healthy subjects(21 µg/L) (P<0.01). The rate of 25OHD(3) deficiency was 79.8% (130/163) in diabetes patients (with and without tuberculosis), and significantly higher than that in healthy subjects 41.3% (33/80), P<0.01. The rate of serious deficiency of 25OHD(3) was 24.1% (20/83) in diabetes patients with tuberculosis. The level of tP(1)NP in diabetes patients (36 µg/L) was significantly lower than that in diabetes patients with tuberculosis 57 µg/L(P<0.01). Conclusions: 25OHD(3) deficiency was common in diabetes patients with and without tuberculosis. The level of tP(1)NP was significantly lower in diabetes patients without tuberculosis than those with tuberculosis, for which further studies were needed .

[Inhibitory effect of DAPT on Notch signaling pathway in curcumin mediated photodynamic therapy for cervical cancer xenografts in nude mice].

Objective: Curcumin was used as photosensitizers in photodynamic therapy on cervical cancer xenografts in nude mice.Analysis the expression changes of Notch and downstream gene as NF-κB and VEGF before and after DAPT inhibition of Notch signaling pathway in vivo experiments.Our aim was to investigate the possible mechanism of Notch signaling pathway in the treatment of cervical cancer with PDT. Methods: A cervical cancer model of nude mice was established by subcutaneous inoculation of human cervical cancer Me180 cells 200 µl.After the success of the model, the experimental animals were divided into 4 groups (model group, curcumin PDT group, simple DAPT group, curcumin-PDT+ DAPT group), each group was 12.Tumor volume changes were analyzed and HE staining was observed in each group.MRNA and protein expression of Notch1 and its downstream NF-κB, VEGF were detected by RT-PCR, immunohistochemistry and Western blot before and after inhibition of Notch signaling pathway by DAPT. Results: Except the control group, the tumor volume of the other three groups remained unchanged or slightly reduced after 1-7 days of treatment.The difference was significant (P<0.05). HE staining showed the most obvious necrosis of curcumin-PDT group with DAPT.Both DAPT and curcumin-PDT could reduce the expression level of Notch1 in mRNA.The inhibition rates were 42.17% and 40.54%, respectively.And the inhibitory effect of curcumin-PDT with DAPT on Notch-1 was the strongest (79.22%) (P<0.01), and two of them had synergistic effect after combination with curcumin-PDT.But the expression of Notch-2 has no obvious inhibitory effect (P>0.05). Both DAPT and curcumin-PDT can inhibit the protein expression of Notch1, NF-κB and VEGF, and two of them have synergistic effect after combined use. Conclusions: DAPT can effectively block the Notch signaling pathway and inhibit the proliferation of cervical cancer cell line Me180.The application of DAPT to inhibit Notch signaling pathway after photodynamic therapy can achieve synergistic effect, which is mainly related to the down-regulation of the expression of Notch1 and NF-κB.Notch signaling pathway may be one of the targets of curcumin-PDT photodynamic therapy.

Synthesis and evaluation of coumarin derivatives against human lung cancer cell lines.

Series of novel coumarin derivatives [I (a-d) and II (a-d)] were successfully synthesized and their structures were determined based on infrared 1H-nuclear magnetic resonance (NMR), HRMS, and single crystal X-ray crystallography. Additionally, the new synthesized compounds were evaluated to identify the molecular characteristics that contribute to their cytotoxicity, which was tested against SK-LU-1, SPC-A-1 and 95D human lung cancer cell lines, using the MTT assay. The results of this study showed that compounds Ic, Id, IIc, and IId exhibited an efficient percentage of inhibition of cell proliferation.

Patient delay in the diagnosis and treatment of tuberculosis in China: findings of case detection projects.

OBJECTIVE: 1) To assess patient delay among new smear-positive pulmonary tuberculosis (PTB) patients in accessing health services in seven FIDELIS (Fund for Innovative DOTS Expansion through Local Initiatives to Stop TB) projects from 2003 to 2008 in China; 2) to compare treatment delay by province; and 3) to assess factors associated with delay. METHOD: Records of new smear-positive PTB patients were reviewed. Data sources were the consultation book, laboratory register, patient record, treatment card and the PWLAHS (people with limited access to health services) evaluation form. Data were collected using a standard questionnaire, cross-checked by staff from the sites and by the International Union Against Tuberculosis and Lung Disease (The Union) and analysed by The Union. RESULTS: Of the 75 401 new smear-positive PTB patients included in the study, 63-89% were PWLAHS. The average gross domestic product of the project sites and at national level were respectively US$557 and US$998. The median patient delay was 93 days (range 68-128). Delays were longer among females, older patients, rural residents and PWLAHS. Delayed access to health services was significantly associated with a greater number of symptoms. CONCLUSION: Patient delay in accessing health care in China was lengthy; TB care and control needs to be improved.

Objectif : Evaluer le délai d'accès aux services des santé de nouveaux patients atteints de tuberculose pulmonaire (TBP) à frottis positif détectés au sein de sept projets FIDELIS (Fund for Innovative DOTS Expansion through Local Initiatives to Stop TB) exécutés en Chine entre 2003 et 2008 ; 2) comparer les retards du traitement par province ; et 3) évaluer les facteurs associés aux retards.Méthode : Les dossiers des patients TPB à frottis positif ont été revus. Les données émanaient du registre des consultations, de celui du laboratoire, des dossiers des patients, des cartes de traitement et des formulaires d'évaluation des personnes ayant un accès limité aux services de santé (PWLAHS). Les données ont été recueillies grâce à un questionnaire standard et vérifiées par le personnel des sites et de l'Union Internationale contre la Tuberculose et les Maladies Respiratoires (L'Union) et analysées par L'Union.Résultats : De 75 401 nouveaux patients atteints de TBP à frottis positif, 63­89% étaient des PWLAHS. Le produit intérieur brut moyen des sites du projet et du niveau national était de 557 et 998 $US respectivement. Le délai médian d'accès aux soins était de 93 jours (extrêmes 68­128). Ce délai était plus long pour les femmes, les patients âgés, les résidents ruraux et ceux estimés être des PWLAHS. Ce délai d'accès aux services était significativement associé à un nombre de symptômes plus élevé.Conclusions : Le délai d'accès aux services de santé en Chine est long et offre des opportunités d'amélioration en matière de lutte contre la TB et de traitement.

Objetivo: 1) Evaluar el retraso en el acceso a los servicios de salud de los pacientes en quienes se diagnosticó tuberculosis pulmonar (TBP) con baciloscopia positiva en siete centros del Proyecto FIDELIS (Fondo para la Expansión Innovadora de DOTS por conducto de Iniciativas Locales a fin de poner Alto a la Tuberculosis) del 2003 al 2008 en la China; 2) comparar el retraso en el tratamiento entre provincias; y 3) evaluar los factores asociados con estos retrasos.Método: Se analizaron las historias clínicas de los pacientes con TBP y baciloscopia positiva. Las fuentes de los datos fueron los libros de consulta, el registro de laboratorio, las historias clínicas, las tarjetas de tratamiento y el formulario de evaluación de las personas con acceso limitado a los servicios de salud. Se recogieron los datos mediante un cuestionario normalizado y verificado que analizaron profesionales de los centros locales y de la Unión contra la Tuberculosis y las Enfermedades Respiratorias.Resultados: Se incluyeron en el estudio 75 401 casos nuevos de TBP con baciloscopia positiva. El producto interno bruto promedio por habitante a escala de los centros del proyecto era 557 USD y a escala nacional era 998 USD. De los pacientes con TB, entre el 63% y el 89% contaban con un acceso limitado a los servicios de salud. La mediana del retraso de los pacientes en acceder a la atención fue 93 días (extremos 68 a 128 días). Los retrasos fueron más prolongados en las mujeres, los pacientes de mayor edad, los residentes en zonas rurales y las personas que se calificaron con un acceso limitado a los servicios sanitarios. El acceso tardío a los servicios de salud se asoció de manera significativa con una mayor cantidad de síntomas.Conclusión: Se observó un retraso considerable de los pacientes para acceder a la atención de salud; esta situación ofrece oportunidades para mejorar la atención y el control de la TB.

Prohibitin 1 gene delivery promotes functional recovery in rats with spinal cord injury.

Spinal cord injury (SCI) represents a severe health problem worldwide usually associated with severe disability and reduced quality of life. The aim of this work was to investigate the role of prohibitin 1 (PHB1) in the progression of SCI in rats. Firstly, we observed that expression of PHB1 was downregulated following SCI in rats. Then, we hypothesized that PHB1 overexpression by delivery of Ad-PHB1 could result in neuroprotection and promote functional recovery following SCI. Briefly, Wistar rats received a 35-g clip-compression injury and were administered Ad-PHB1 or Ad immediately following SCI. It was found that Ad-PHB1 administration significantly improved locomotor function and increased pain tolerance in rats with SCI. Furthermore, Ad-PHB1 administration following SCI attenuated axonal degradation and increased neuron sparing. Ad-PHB1 administration following SCI reduced apoptosis through inhibiting the Bcl-2/Bax/caspase-3 pathway. Ad-PHB1 administration following SCI suppressed endoplasmic reticulum stress, evidenced by reduced mRNA levels of CCAAT enhancer binding protein homologous protein, chaperone-ucose-regulated protein 78, and X-box protein 1. Ad-PHB1 administration following SCI restored mitochondrial adenosine triphosphate formation, reduced reactive oxygen species formation, and improved mitochondrial respiration rates. Finally, Ad-PHB1 administration following SCI activated downstream signals including phosphatidylinositol-3-kinase (PI3K)/Akt, extracellular signal-regulated kinase (ERK1/2), and nuclear factor-kappaB. These data indicate that the PHB1 plays an important role in the development of SCI and might provide a therapeutic target to promote recovery from SCI.

Development of EST-SSR markers related to salt tolerance and their application in genetic diversity and evolution analysis in Gossypium.

Salt stress is becoming one of the major problems in global agriculture with the onset of global warming, an increasing scarcity of fresh water, and improper land irrigation and fertilization practices, which leads to reduction of crop output and even causes crop death. To speed up the exploitation of saline land, it is a good choice to grow plants with a high level of salt tolerance and economic benefits. As the leading fiber crop grown commercially worldwide, cotton is placed in the moderately salt-tolerant group of plant species, and there is promising potential to improve salt tolerance in cultivated cotton. To facilitate the mapping of salt-tolerant quantitative trait loci in cotton so as to serve the aims of salt-tolerant molecular breeding in cotton, it is necessary to develop salt-tolerant molecular markers. The objective of this research was to develop simple sequence repeat (SSR) markers based on cotton salt-tolerant expressed sequence tags. To test the efficacy of these SSR markers, their polymorphism and cross-species transferability were evaluated, and their value was further investigated on the basis of genetic diversity and evolution analysis.

Sequential, timely and controlled expression of hVEGF165 and Ang-1 effectively improves functional angiogenesis and cardiac function in vivo.

We aimed to control the gene expression of vascular endothelial growth factor (VEGF) and angiopoietin-1 (Ang-1) in the ischemic heart to explore the feasibility of sequential, timely and controlled multigene expression as a means of improving therapeutic angiogenesis in vivo. Adult rabbit myocardial infarction models were surgically established (n=120). Hypoxia-inducible factor-1α-hypoxic response element (HIF1α-HRE) and Tet (tetracycline)-On advanced gene control systems were reconstructed for controlled expression of the human VEGF165 (hVEGF165) and Ang-1 genes, respectively. Recombinant adeno-associated viruses (rAAV)-9HRE-hVEGF165 and rAAV-TRE-Tight-Ang-1 were delivered into the ischemic myocardium for 12 weeks. Reverse transcription-polymerase chain reaction, western blotting and immunofluorescence staining were used to detect gene and protein expression. Vessel functionality, vascular permeability and animal cardiac function were also evaluated. Under the control of the HIF1α-HRE and Tet-On gene control systems, the expression of the exogenous hVEGF165 and Ang-1 genes was consistent in the ischemia control. In the sequential group, we found that the number of functional vessels with a larger diameter and more vascular branches was increased, and vascular permeability was significantly reduced. In addition, animal heart function was significantly improved compared with the non-sequential and hVEGF165- or Ang-1-only groups (P<0.05, P<0.05, respectively). Sequential, timely and controlled expression of the hVEGF165 and Ang-1 genes in vivo is a new therapeutic angiogenesis strategy that can effectively promote functional vessel regeneration and can improve cardiac function in ischemic heart disease.

Isolation and characterization of Streptomyces spp. strains F-6 and F-7 capable of decomposing alkali lignin.

Biodegradation and bioconversion of lignin are the result of the combined action of fungi, bacteria and actinomycetes. Through screening from forest soil, two novel isolated actinomycete strains were identified as Streptomyces spp. strains F-6 and F-7 by their morphology, cultural characteristics and high homology to the 16S rRNA gene. Both strains possessed laccase and manganese peroxidase activities. Laccase activity produced by strain F-6 was up to 935.4 U g(-1) dry cell weight. More than 50% of alkali lignin was removed by strains F-6 and F-7 in 12 days of incubation. GC-MS analysis of the biodegraded products showed strain F-6 converted lignin into phenol and broken phenol compounds. The two strains could co-culture with white-rot fungus, and the combined actinonycete-fungus system decomposed alkali lignin effectively.

Prediction of RNA-binding proteins by voting systems.

It is important to identify which proteins can interact with RNA for the purpose of protein annotation, since interactions between RNA and proteins influence the structure of the ribosome and play important roles in gene expression. This paper tries to identify proteins that can interact with RNA using voting systems. Firstly through Weka, 34 learning algorithms are chosen for investigation. Then simple majority voting system (SMVS) is used for the prediction of RNA-binding proteins, achieving average ACC (overall prediction accuracy) value of 79.72% and MCC (Matthew's correlation coefficient) value of 59.77% for the independent testing dataset. Then mRMR (minimum redundancy maximum relevance) strategy is used, which is transferred into algorithm selection. In addition, the MCC value of each classifier is assigned to be the weight of the classifier's vote. As a result, best average MCC values are attained when 22 algorithms are selected and integrated through weighted votes, which are 64.70% for the independent testing dataset, and ACC value is 82.04% at this moment.

Isolation and characterization of a fungus Aspergillus sp. strain F-3 capable of degrading alkali lignin.

A fungus strain F-3 was selected from fungal strains isolated from forest soil in Dalian of China. It was identified as one Aspergillus sp. stain F-3 with its morphologic, cultural characteristics and high homology to the genus of rDNA sequence. The budges or thickened node-like structures are peculiar structures of hyphae of the strain. The fungus degraded 65% of alkali lignin (2,000 mg l(-1)) after day 8 of incubation at 30°C at pH 7. The removal of colority was up to 100% at 8 days. The biodegradation of lignin by Aspergillus sp. F-3 favored initial pH 7.0. Excess acid or alkali conditions were not propitious to lignin decomposing. Addition of ammonium L: -tartrate or glucose delayed or repressed biodegradation activities. During lignin degradation, manganese peroxidase (28.2 U l(-1)) and laccase (3.5 U l(-1))activities were detected after day 7 of incubation. GC-MS analysis of biodegraded products showed strain F-3 could convert alkali lignin into small molecules or other utilizable products. Strain F-3 may co-culture with white rot fungus and decompose alkali lignin effectively.

Protective effect of melatonin against gentamicin ototoxicity.

OBJECTIVE: To research the protective effect of melatonin against gentamicin ototoxicity. METHODS: Guinea pigs were randomly divided into four groups. The first group received intramuscular gentamicin (120 mg/kg body weight/day) for 17 days. Over the same time period, a second group simultaneously received intramuscular gentamicin (120 mg/kg body weight/day) plus (on the other side) intramuscular melatonin (0.3 ml kg body weight/day). Two groups of controls were treated for 17 days with either intramuscular melatonin or intramuscular saline. After the 17 days, each animal underwent distortion product otoacoustic emission testing (both ears). The guinea pigs were sacrificed by decapitation just after the final injection. Their cochleae were used to produce a tissue section, surface preparation and scanning electron microscope preparation. RESULTS: Distortion product otoacoustic emission testing indicated gentamicin-induced hearing loss at 3, 4, 6 and 8 kHz in gentamicin-treated animals. Animals receiving melatonin co-therapy had significantly attenuated hearing loss and their cochleae showed lower rates of outer hair cell loss (comparing the same cochlear turns), compared with gentamicin-treated animals (p < 0.01). CONCLUSION: These findings confirm the occurrence of outer hair cell loss after gentamicin treatment, and the attenuation of such loss following simultaneous melatonin injection, using the method of morphological evaluation. These results suggest that melatonin protects against gentamicin ototoxicity by interfering with cytotoxic mechanisms.

Dual silencing of type 1 insulin-like growth factor and epidermal growth factor receptors to induce apoptosis of nasopharyngeal cancer cells.

OBJECTIVE: The epidermal growth factor receptor (EGFR) and type 1 insulin-like growth factor receptor (type 1 IGF receptor or IGF1R) have played an important role in the growth and apoptosis of cancer. The RNA interference (RNAi) technique can suppress gene expression, but the effects of dual silencing of EGFR and type 1 IGF receptor have not been well understood. METHODS: pU6-EGFR-shRNA-1, pU6-EGFR-shRNA-2, pU6-IGF1R-shRNA-1 and pU6-IGF-1R-shRNA-2 plasimd vectors were transfected to the nasopharyngeal cancer cells. Seven groups were selected for the study. The protein and downstream protein expression were assessed by Western blot. Apoptosis was determined via flow cytometry. Meanwhile, chemosensitivity of nasopharyngeal cancer cell lines transfeced to chemotherapeutic drugs were carried out by MTT. RESULTS: In dual silencing of EGFR and IGF-1R, the protein expression much more was decreased than single silencing of EGFR or IGF-1R, but the cell apoptosis much more is increased than single silencing EGFR or IGF-1R. Dual silencing of EGFR and IGF-1R enhanced chemosensitivity to anticancer drugs, compared with single silencing of EGFR or IGF-1R. CONCLUSION: Dual silencing of EGFR and IGF-1R are capable of suppressing EGFR and IGF-1R expression of the nasopharyngeal cancer cell and can promote apoptosis and increase the cell sensitivity of anticancer drug. The dual silencing of genes RNAi technique is significantly better than a single gene.

Platelet adhesion onto segmented polyurethane surfaces modified by carboxybetaine.

Polyurethanes are widely used as blood-contacting biomaterials due to their good biocompatibility and mechanical properties. Nevertheless, their blood compatibility is still not adequate for more demanding applications. Surface modification is an effective way to improve the hemocompatibility for biomaterials. The purpose of present study was to synthesize a novel nonthrombogenic biomaterial by modifying the surface of polyurethane with Zwitterions of carboxybetaine monomer. The films of polyurethane were grafted with two kinds of carboxybetaine by a three-step procedure. In the first step, the film surfaces were treated with hexamethylene diisocyanate (HDI) in toluene at 50 degrees C in the presence of di-n-butyl tin dilaurate (DBTDL) as a catalyst. The extent of the reaction was measured by ATR-FT-IR spectra: a maximum number of free NCO group was obtained after a reaction time of 90 min. In the second step, the hydroxyl group of N,N-dimethylethylethanolamine (DMEA) or 4-dimethylamino-1-butanol (DMBA) was allowed to react in toluene with isocyanate groups bound on surface. In the third step, carboxybetaines were formed in the surface through the ring-opening reaction between tertiary amine of DMEA or DMBA and beta-propiolactone (PL). It was characterized by ATR-FT-IR and XPS that the grafted surfaces were composed of carboxybetaine. The results of the contact angle measurements showed that they were strongly hydrophilic. Platelet adhesion tests showed that films grafted carboxybetaine have good blood compatibility, as featured by the low platelet adhesion.

Grafting sulfobetaine monomer onto the segmented poly(ether-urethane) surface to improve hemocompatibility.

Polyurethanes are widely used as blood-contacting biomaterials, due to their good biocompatibility and mechanical properties. Nevertheless, their blood compatibility is still not adequate for more demanding applications. Surface modification is an effective way to improve the hemocompatibility for biomaterials. The purpose of the present study was to synthesize a novel nonthrombogenic biomaterial by modifying the surface of polyurethane. Ozonization was used to introduce active peroxide groups onto the segmented poly(ether-urethane) (SPEU) film surface and graft polymerization of N,N'-dimethyl (methacryloyloxyethyl) ammonium propanesulfonate (DMAPS), a sulfobetaine structure, onto the ozone-activated SPEU surface was conducted. The SPEU-g-PDMAPS film was characterized by ATR-FTIR, XPS, and contact angle measurements. ATR-FTIR and XPS confirmed the graft polymerization. The grafted film possessed a relatively hydrophilic surface, as revealed by contact angle measurement. The blood compatibility of the grafted films was evaluated by a platelet-rich plasma (PRP) adhesion study and scanning electron microscopy, using SPEU film as the reference. No platelet adhesion was observed for the grafted films incubated with PRP at 37 degrees C for 60 and 180 min. This new sulfobetaine structure grafted biomaterial might have potential for biomedical applications.

Studies of the inheritance of seed qualities and the exploitation of F2 heterosis in low gossypol strains in upland cotton.

Twenty cross combinations were made with 4 recessive glandless lines (gl2gl2 gl3gl3) used as females and 5 dominant glandless lines (Gl2eGl2e Gl3Gl3) used as male parents to estimate the genetic variance components of kernel oil and protein content of seeds, oil and protein index, and kernel index using a genetic model for parents, F2 and F3. The results showed that all the analyzed traits were mainly controlled by additive effects. Oil content was controlled mainly by maternal additive effect, and other traits by direct additive effect. The average heterosis of F2 over mid-parent based on population mean was -1.99% to 1.11% for all these traits. It suggests that little inbreeding depression exists for F2 and F3 seeds. There were 75% and 60% of the F2 and the F3 combinations in which open-pollinated seeds contained gossypol levels lower than 0.4 gkg-1. This result indicated that it is possible to screen and select high yielding F2 hybrids with a gossypol content lower than the regulated criterion and without lowering seed quality.